RESUMO
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by a chronic inflammatory state that plays a relevant role in the disease pathogenesis (as proven by high levels of inflammatory cytokines with prognostic significance and by a persistent oxidative stress) and by extensive neoangiogenesis in bone marrow (BM) and spleen. Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in patients with cancer, sepsis or chronic inflammation, favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. In this paper, we evaluated the presence of circulating MDSCs in PMF patients, the plasmatic factors involved in their mobilization/expansion and the correlations with laboratory, genetic and clinical parameters. The data indicated that MDSCs could have a relevant role in PMF as a new pathogenic mechanism contributing to explaining the phenotypic diversity observed during the clinical course of the disease, or a potential new target for personalized treatment.
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We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1ß and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.
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Hemangioma , Células-Tronco Mesenquimais , Humanos , Propranolol/farmacologia , Propranolol/uso terapêutico , Propranolol/metabolismo , Transcriptoma , Células-Tronco Mesenquimais/metabolismo , Adipogenia/genética , Hemangioma/genética , Hemangioma/tratamento farmacológico , Hemangioma/metabolismoRESUMO
INTRODUCTION: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. METHODS: We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). RESULTS: 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of JAK2V617F compared with persons with PMF (55% vs. 70%; p < 0.001) and higher frequencies of CALR mutations (37% vs. 17%; p < 0.001). They also had lower frequency of variations associated with JAK2V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p < 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); p < 0.001). CONCLUSION: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.
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Transtornos Mieloproliferativos , Neoplasias , Mielofibrose Primária , Trombocitemia Essencial , Trombocitose , Feminino , Humanos , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Megacariócitos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Trombocitose/genética , Fenótipo , Janus Quinase 2/genética , Calreticulina/genéticaRESUMO
Different bodies of evidence support the existence of a common origin of hematopoietic and endothelial lineages; moreover, recent studies have indicated the presence of a hemogenic endothelium and a common hemato-endothelial precursor both in the embryo and in the cord blood. Conversely, to our knowledge, there is no evidence of such bipotential cells in human postnatal tissues or blood. In this study, we investigated the presence and phenotype of "transitional" cells in different tissues of patients with primary myelofibrosis (PMF). Using confocal microscopy and flow cytometry, we identified a rare cell population in the bone marrow and spleen of patients with PMF, which coexpresses the endothelial marker CD144 (vascular endothelial (VE)-cadherin), the pan-hematopoietic marker CD45, the early myeloid marker CD33, and CD34, a common endothelial and hematopoietic antigen.
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Hemangioblastos , Mielofibrose Primária , Humanos , Medula Óssea , Baço , Antígenos CD34 , Biomarcadores , Células da Medula Óssea , Diferenciação CelularRESUMO
INTRODUCTION: In 1991, we reported 18 persons with a clinical-pathologic entity and termed atypical myeloproliferative disorder because they did not meet the contemporary diagnostic criteria for a myeloproliferative neoplasm. We sought to gain further knowledge on this disease entity. METHODS: This retrospective cohort study included consecutive subjects registered in the database of the Center for the Study of Myelofibrosis in Pavia, Italy, from 1998 to 2020 (June), and diagnosed with atypical myeloproliferative disorder according to our adjudicated criteria. We studied clinical, histological, cytogenetic, and molecular covariates and risks of thrombosis, disease progression, and death. Data were compared with those of concurrent subjects with prefibrotic myelofibrosis. RESULTS: Fifteen new subjects with atypical myeloproliferative disorder were identified. Seven were male. Median age was 50 years (IQR, 41-54 years). Thirteen were diagnosed with a synchronous symptomatic or incidentally detected thrombotic event. The bone marrow showed megakaryocyte hyperplasia with dysplasia. JAK2V617F was present in 10 subjects and CALR mutation in one. No other somatic mutations were identified in next generation sequencing. After a median follow-up of 101 months (IQR, 40-160 months), no subject had disease progression or blast transformation. Incidence of post-diagnosis or recurrent thrombosis was 3.9 events (95% confidence interval, 3.5-4.0) and 5.0 events (4.6-5.6) per 100 person-years. Features of subjects with atypical myeloproliferative disorder differed markedly from those of 546 subjects with prefibrotic myelofibrosis. CONCLUSION: Our data indicate that these 15 persons have a distinct myeloproliferative neoplasm. We propose naming this new disorder clonal megakaryocyte dysplasia with normal blood values.
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Calreticulina , Neoplasias Hematológicas , Janus Quinase 2 , Megacariócitos , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos , Adulto , Substituição de Aminoácidos , Medula Óssea/metabolismo , Medula Óssea/patologia , Calreticulina/genética , Calreticulina/metabolismo , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Masculino , Megacariócitos/metabolismo , Megacariócitos/patologia , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Estudos Retrospectivos , TromboseRESUMO
Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such as proliferation, differentiation, and immunomodulatory capacities. MSCs were in vitro expanded from the BM of 57 AL patients and 14 healthy donors (HDs). MSC surface markers were analyzed by flow cytometry, osteogenic and adipogenic differentiation capacities were in vitro evaluated, and co-culture experiments were performed in order to investigate MSC immunomodulatory properties towards the ALMC-2 cell line and HD peripheral blood mononuclear cells (PBMCs). AL-MSCs were comparable to HD-MSCs for morphology, immune-phenotype, and differentiation capacities. AL-MSCs showed a reduced proliferation rate, entering senescence at earlier passages than HD-MSCs. The AL-MSC modulatory effect on the plasma-cell line or circulating plasma cells was comparable to that of HD-MSCs. To our knowledge, this is the first study providing a comprehensive characterization of AL-MSCs. It remains to be defined if the observed abnormalities are the consequence of or are involved in the disease pathogenesis. BM microenvironment components in AL may represent the targets for the prevention/treatment of the disease in personalized therapies.
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Background Single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A ( VEGFA ) are associated with susceptibility to several diseases including cancer. Correlations between VEGFA rs3025020 genotypes with clinical and laboratory features of primary myelofibrosis (PMF) are unstudied. Methods DNA was analyzed by real-time polymerase chain reaction for VEGFA rs3025020 genotypes in a cohort of 844 subjects with PMF and in two cohorts of normal subjects ( N = 247 and N = 107). Results Frequency of rs3025020 minor allele (T) was not significantly different in subjects with PMF compared with normals; however, the T-allele was more frequent in PMF subjects with a calreticulin ( CALR )-mutated genotype compared with normals (35 vs. 27%; OR = 1.47 [95% CI, 1.09, 1.98] p = 0.011), especially in subjects with a CALR- type 2/type 2-like mutation (43 vs. 27%; OR = 2.01 [1.25, 3.24] p = 0.004). CALR mutants with the rs3025020 TT genotype had higher CXCR4 expression on CD34-positive blood cells, and those who carried CT/TT genotypes had lower platelet concentrations compared with other genotypes at diagnosis. Overall, subjects with the rs3025020 CT/TT genotype had a lower cumulative incidence of deep vein thrombosis in typical sites (1.6 vs. 4.2%; OR = 0.37 [0.15, 0.90] p = 0.029) and longer interval from diagnosis to first thrombosis (HR = 0.37 [0.14, 0.95] p = 0.039). Conclusion Persons with PMF and the VEGFA rs3025020 minor T-allele are more likely to have a CALR mutation compared with other somatic driver mutations and lower cumulative incidence and hazard for deep vein thrombosis in typical sites.
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Biomarcadores Tumorais/genética , Fibrose/complicações , Fenótipo , Polimorfismo de Nucleotídeo Único , Mielofibrose Primária/complicações , Trombose/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Feminino , Fibrose/genética , Fibrose/patologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Mielofibrose Primária/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Trombose/etiologia , Trombose/metabolismoRESUMO
We evaluated the association of VEGFA rs3025039 polymorphism with clinical co-variates and outcomes in 849 subjects with primary myelofibrosis (PMF) and 250 healthy controls. Minor T-allele frequency was higher in subjects with JAK2V617F compared with those without JAK2V617F (18% vs. 13%; p = 0.014). In subjects with JAK2V617F, the TT genotype was associated at diagnosis with lower platelet concentrations (p = 0.033), higher plasma LDH concentration (p = 0.005), higher blood CD34-positive cells (p = 0.027), lower plasma cholesterol concentration (p = 0.046), and higher concentration of high-sensitivity C-reactive protein (p = 0.018). These associations were not found in subjects with PMF without JAK2V617F. In subjects with the TT genotype, risk of death was higher compared with subjects with CC/CT genotypes (HR = 2.12 [1.03, 4.35], p = 0.041). Finally, the TT genotype was associated with higher frequency of deep vein thrombosis in typical sites (12.5% vs. 2.5%; OR = 5.46 [1.51, 19.7], p = 0.009). In conclusion, in subjects with PMF, the VEGFA rs3025039 CT or TT genotypes are more common in those with JAK2V617F than in those without JAK2V67F mutation and are associated with disease severity, poor prognosis, and risk of deep vein thrombosis.
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Predisposição Genética para Doença , Mielofibrose Primária/genética , Fator A de Crescimento do Endotélio Vascular/genética , Trombose Venosa/genética , Alelos , Análise Citogenética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único/genética , Mielofibrose Primária/complicações , Mielofibrose Primária/patologia , Trombose Venosa/complicações , Trombose Venosa/patologiaRESUMO
The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). A cutoff value of 39% was associated with a diagnosis of pre-fibrotic PMF vs. ET with a positive predictive value of 97%. In PMF male sex, older age, and MPL mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin < 100 g/L, CD34-positive blood cells > 50 × 106/L, and CD34/CXCR4-se <39% at diagnosis. The model identified three risk cohorts with greater accuracy compared with the International Prognostic Scoring System. In conclusion, CD34/CXCR4-se is a highly sensitive marker of disease activity and a new potential diagnostic and prognostic biomarker in PMF.
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Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Células Sanguíneas/metabolismo , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/metabolismo , Receptores CXCR4/metabolismo , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Transdução de Sinais , Taxa de SobrevidaRESUMO
The frequency of A3669G single nucleotide polymorphism (SNP) of human glucocorticoid receptor has been reported increased in polycythemia vera. We investigated the frequency of A3669G SNP and its impact on disease phenotype and progression in 499 patients with primary myelofibrosis (PMF). The distribution of the A3669G allele differed between PMF patients and 2 healthy control populations (odds ratio, 1.6 and 1.8). The variant allele at the homozygous state (G/G) was associated with higher white blood cell count, larger spleen index, and higher frequency of circulating CD34(+) cells at diagnosis. The latter association remained significant after correction for the JAK2V617F genotype. In patients JAK2V617F mutated, the G/G genotype was associated with shorter overall survival (77.6 months vs 298 months, P = .049) and blast transformation (BT)-free survival (76.7 months vs 261 months; P = .018). The latter association remained significant after correction for the known BT risk factors, such as age, sex, white blood cell count, percentage of blasts, IPSS prognostic score, and homozygosity for JAK2V617F (hazard ratio = 3.3; P = .006). In conclusion, the glucocorticoid receptor A3669G is a susceptibility allele for PMF: it contributes to confer the phenotype of excess myeloproliferation, and it cooperates with the JAK2V617F mutation in determining BT.
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Predisposição Genética para Doença , Ativação Linfocitária/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Mielofibrose Primária/genética , Receptores de Glucocorticoides/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Mielofibrose Primária/mortalidade , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: In the WHO diagnostic classification, prefibrotic myelofibrosis (pre-MF) is included in the category of primary myelofibrosis (PMF). However, strong evidence for this position is lacking. PATIENTS AND METHODS: We investigated whether pre-MF may be aligned along a clinical and biological continuum in 683 consecutive patients who received a WHO diagnosis of PMF. RESULTS: As compared with PMF-fibrotic type, pre-MF (132 cases) showed female dominance, younger age, higher hemoglobin, higher platelet count, lower white blood cell count, smaller spleen index and higher incidence of splanchnic vein thrombosis. Female to male ratio and hemoglobin steadily decreased, while age increased from pre-MF to PMF- fibrotic type with early and to advanced bone marrow (BM) fibrosis. Likely, circulating CD34+ cells, LDH levels, and frequency of chromosomal abnormalities increased, while CXCR4 expression on CD34+ cells and serum cholesterol decreased along the continuum of BM fibrosis. Median survival of the entire cohort of PMF cases was 21 years. Ninety-eight, eighty-one and fifty-six percent of patients with pre-MF, PMF-fibrotic type with early and with advanced BM fibrosis, respectively, were alive at 10 years from diagnosis. CONCLUSION: Pre-MF is a presentation mode of PMF with a very indolent phenotype. The major consequences of this contention is a new clinical vision of PMF, and the need to improve prognosis prediction of the disease.
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Mielofibrose Primária/classificação , Mielofibrose Primária/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Janus Quinase 2/genética , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Fenótipo , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Prognóstico , Organização Mundial da Saúde , Adulto JovemAssuntos
Predisposição Genética para Doença , Janus Quinase 2/genética , Oclusão Vascular Mesentérica/genética , Transtornos Mieloproliferativos/genética , Trombose Venosa/genética , Neoplasias da Medula Óssea/genética , Estudos de Casos e Controles , Proteínas de Fusão bcr-abl/genética , Frequência do Gene , Haplótipos , Humanos , Janus Quinase 2/fisiologia , Veias Mesentéricas , Mutação , Fenilalanina/genética , Polimorfismo Genético/fisiologia , Polimorfismo de Nucleotídeo Único , Circulação Esplâncnica/genética , Valina/genéticaRESUMO
BACKGROUND: Epidemiologic evidence related to asthma control in patients from the general population is scanty. OBJECTIVES: We sought to assess asthma control in several European centers according to the Global Initiative for Asthma (GINA) guidelines and to investigate its determinants. METHODS: In the European Community Respiratory Health Survey II (1999-2002), 1241 adults with asthma were identified and classified into inhaled corticosteroid (ICS) users and non-ICS users in the last year. Control was assessed in both groups by using the GINA proposal (controlled, partly controlled, and uncontrolled asthma), and it was related to potential determinants. RESULTS: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their asthma under control; individuals with uncontrolled asthma accounted for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%), respectively. Among ICS users, the prevalence of uncontrolled asthma showed great variability across Europe, ranging from 20% (95% CI, 7% to 41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species were associated with poor control in ICS users. About 65% and 87% of ICS users with uncontrolled and partly controlled asthma, respectively, were on a medication regimen that was less than recommended by the GINA guidelines. CONCLUSION: Six of 7 European asthmatic adults using ICSs in the last year did not achieve good disease control. The large majority of subjects with poorly controlled asthma were using antiasthma drugs in a suboptimal way. A wide variability in asthma control emerged across Europe. CLINICAL IMPLICATIONS: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines.
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Asma/tratamento farmacológico , Asma/epidemiologia , Gerenciamento Clínico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Alérgenos/efeitos adversos , Animais , Asma/diagnóstico , Estudos Transversais , União Europeia , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto/normas , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The objective was to analyze the frequency and factors influencing necrotic complication in female patients undergoing nipple- and areola-sparing mastectomy. Nipple- and areola-sparing mastectomy has recently been shown to yield satisfactory results in a carefully selected group of breast cancer patients. The technique includes extensive undermining of the nipple-areola complex, which may result in an increased rate of necrotic complications. We report our early experience with necrotic changes after nipple- and areola-sparing mastectomy. METHODS: The medical records of 38 patients undergoing nipple- and areola-sparing mastectomy were analyzed retrospectively. RESULTS: Mean age of the patient was 44.5 years (range 26-65). Necrotic complications occurred in 15.8% of patients and included: skin flap necrosis (1 case), partial nipple-areola complex necrosis (2 cases), and complete nipple-areola complex necrosis (3 cases). Two cases of capsular contraction were also recorded. Statistical analysis showed age below 45 years to be associated with a lower risk of necrotic complications (OR 4.51, P<0.05). CONCLUSIONS: The nipple- and areola-sparing mastectomy, although resulting in a relatively high frequency of necrotic complications, is a valuable surgical option for patients with small, peripheral tumors and for women undergoing prophylactic mastectomy. The procedure seems to be safer for women under 45 years of age.
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Mastectomia/efeitos adversos , Mamilos/patologia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Necrose/etiologia , Mamilos/irrigação sanguínea , Estudos RetrospectivosRESUMO
BACKGROUND: The natural history of asthma severity is poorly known. OBJECTIVE: To investigate prognostic factors of asthma severity. METHODS: All current patients with asthma identified in 1991 to 1993 in the European Community Respiratory Health Survey were followed up, and their severity was assessed in 2002 by using the Global Initiative for Asthma categorization (n = 856). Asthma severity (remittent, intermittent, mild, moderate, severe) was related to potential determinants evaluated at baseline and during the follow-up by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios (RRRs). RESULTS: Asthma severity measured at baseline was a determinant of a patient's severity at the end of the follow-up. At baseline, severe persistent had a poorer FEV1% predicted, a poorer symptom control, higher IgE levels (RRR, 2.06; 95% CI, 1.38-3.06), and a higher prevalence of chronic cough/mucus hypersecretion (RRR, 4.90; 95% CI, 2.18-11.02) than patients with intermittent asthma. Moderate persistent showed the same prognostic factors as severe persistent, even if the associations were weaker. Mild persistent had a distribution of prognostic factors that was similar to patients with intermittent asthma, although the former showed a poorer symptom control than the latter. Remission mainly occurred in patients with less severe asthma and was negatively associated with a change in body mass index (RRR, 0.86; 95% CI, 0.75-0.97). Allergic rhinitis, smoking, and respiratory infections in childhood were not associated with asthma severity. CONCLUSION: Patients with moderate and severe persistent asthma are characterized by early deterioration of lung function. High IgE levels and persistent cough/mucus hypersecretion are strong markers of moderate/severe asthma, which seems to be a different phenotype from mild persistent or intermittent asthma. CLINICAL IMPLICATIONS: Our results suggest that the evolution of asthma severity is to a large extent predictable.
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Asma/diagnóstico , Índice de Gravidade de Doença , Adulto , Asma/fisiopatologia , Índice de Massa Corporal , Estudos de Coortes , Europa (Continente) , Feminino , Seguimentos , Humanos , Internacionalidade , Masculino , Estudos Multicêntricos como Assunto , Prognóstico , Estudos ProspectivosRESUMO
AIMS: There are few data on the outcomes of cardiac arrest (CA) victims when the defibrillation capability of broad rural and urban territories is fully operated by volunteers and laypersons. METHODS AND RESULTS: In this study, we investigated whether a programme based on diffuse deployment of automated external defibrillators (AEDs) operated by 2186 trained volunteers and laypersons across the County of Brescia, Italy (area: 4826 km(2); population: 1 112 628), would safely and effectively impact the current survival among victims of out-of-hospital CA. Forty-nine AEDs were added to the former emergency medical system that uses manual EDs in the emergency department of 10 county hospitals and in five medically equipped ambulances. The primary endpoint was survival free of neurological impairment at 1-year follow-up. Data were analysed in 692 victims before and in 702 victims after the deployment of the AEDs. Survival increased from 0.9% (95% CI 0.4-1.8%) in the historical cohort to 3.0% (95% CI 1.7-4.3%) (P=0.0015), despite similar intervals from dispatch to arrival at the site of collapse [median (quartile range): 7 (4) min vs. 6 (6) min]. Increase of survival was noted both in the urban [from 1.4% (95% CI 0.4-3.4 %) to 4.0% (95% CI 2.0-6.9 %), P=0.024] and in the rural territory [from 0.5% (95% CI 0.1-1.6%) to 2.5% (95% CI 1.3-4.2%), P=0.013]. The additional costs per quality-adjusted life year saved amounted to euro39 388 (95% CI euro16 731-49 329) during the start-up phase of the study and to euro23 661 (95% CI euro10 327-35 528) at steady state. CONCLUSION: Diffuse implementation of AEDs fully operated by trained volunteers and laypersons within a broad and unselected environment proved safe and was associated with a significantly higher long-term survival of CA victims.
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Automação , Cardioversão Elétrica/instrumentação , Serviços Médicos de Emergência/normas , Tratamento de Emergência/instrumentação , Parada Cardíaca/terapia , Cardioversão Elétrica/normas , Emergências , Tratamento de Emergência/normas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , VoluntáriosRESUMO
AIM: To point out the degree of satisfaction of psychotic patients and their family members in relation to the assistance given by the four Outpatient Mental Health Services in the Savona Department. METHODS: patients with a diagnosis of psychosis were selected among those visited during the period from the 1st of January to the 30th of April 2002. VSSS-54 item, was utilized. RESULTS: The analysis, conducted on 301 patients and 149 family members, highlighted: 1) a substantially positive assessment of the Services 2) the patients and their family members quite agreed on the evaluation of the different areas of satisfaction 3) Strong points: all the operators' human and professional skills 4) request of a better knowledge of the Service's programmes and more information to the public opinion 5) request of more collaboration with family doctors and other specialists 6) The worst criticism: the Service's response to night and holiday emergency. CONCLUSIONS: The patients and their family members reacted positively to the survey, that created more resistance on the part of the operators. The survey is not to be considered the final objective, but the point of departure for a new form of collaboration between the users and the operators.